Effect of 2 Doses of EPA on Apoptosis and Cell Proliferation on Colon Mucosa

This study has been completed.
Sponsor:
Information provided by:
S.L.A. Pharma AG
ClinicalTrials.gov Identifier:
NCT00432913
First received: February 7, 2007
Last updated: October 16, 2008
Last verified: October 2008
  Purpose

The purpose of this study is to determine the effect of two doses purified EPA (an omega-3 fatty acid), on apoptosis (natural cell death) and cell proliferation (formation of new cells) in the lining of the colon for patients with a history of colonic polyps.


Condition Intervention Phase
Adenomatous Polyps
Drug: Eicosapentaenoic Acid (EPA)
Procedure: Endoscopy
Procedure: Biopsies taken
Procedure: Clinical chemistry
Procedure: Haematology
Procedure: Physical examination
Procedure: Vital signs
Procedure: Urine pregnancy test
Procedure: Completion of patient diary card
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Two Dose Levels of Eicosapentaenoic Acid (EPA) on Apoptosis and Cell Proliferation in the Colonic Mucosa of Patients With a History of Colonic Polyps.

Resource links provided by NLM:


Further study details as provided by S.L.A. Pharma AG:

Primary Outcome Measures:
  • To measure levels of apoptosis in the normal colonic mucosa in subjects with a history of colonic adenomas, before and after treatment with EPA 99%. [ Time Frame: 3 months and 6 months ]
  • To measure levels of cell proliferation in the normal colonic mucosa in subjects with a history of colonic adenomas, before and after treatment with EPA 99%. [ Time Frame: 3 months and 6 months ]

Secondary Outcome Measures:
  • To measure the tissue content of EPA in the colonic mucosa before, during and after treatment with EPA. [ Time Frame: 3 months and 6 months ]
  • To determine the safety and tolerability of EPA. [ Time Frame: 3 months and 6 months ]

Estimated Enrollment: 120
Study Start Date: October 2006
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1g EPA per day Drug: Eicosapentaenoic Acid (EPA)
Either 2 x 500mg EPA capsules in the morning and evening (2g per day EPA) or 1 x 500mg EPA and 1 x placebo in the morning and evening (1g per day EPA)
Other Name: ALFA
Procedure: Endoscopy
At baseline, month 3 and month 6.
Other Names:
  • Colonoscopy
  • Flexible sigmoidoscopy
Procedure: Biopsies taken
9 biopsies taken for measurement of apoptosis (3 biopsies), cell proliferation (3 biopsies) and fatty acid levels (3 biopsies) at baseline, month 3 and month 6.
Procedure: Clinical chemistry
Full blood count at baseline, month 3 and month 6.
Procedure: Haematology
Urea and electrolytes, liver function tests, clotting profile and CRP at baseline, month 3 and month 6.
Procedure: Physical examination
Including cardio-respiratory and abdominal examination at baseline, month 3 and month 6.
Procedure: Vital signs
Height, weight, heart rate, blood pressure and temperature at baseline, month 3 and month 6.
Procedure: Urine pregnancy test
For subjects of child-bearing potential, urine pregnancy test at baseline, month 3 and month 6.
Procedure: Completion of patient diary card
Subjects are requested to complete when study medication is taken and in any new or unusual symptoms are experienced on a daily basis for 6 months.
Active Comparator: 2g EPA per day Drug: Eicosapentaenoic Acid (EPA)
Either 2 x 500mg EPA capsules in the morning and evening (2g per day EPA) or 1 x 500mg EPA and 1 x placebo in the morning and evening (1g per day EPA)
Other Name: ALFA
Procedure: Endoscopy
At baseline, month 3 and month 6.
Other Names:
  • Colonoscopy
  • Flexible sigmoidoscopy
Procedure: Biopsies taken
9 biopsies taken for measurement of apoptosis (3 biopsies), cell proliferation (3 biopsies) and fatty acid levels (3 biopsies) at baseline, month 3 and month 6.
Procedure: Clinical chemistry
Full blood count at baseline, month 3 and month 6.
Procedure: Haematology
Urea and electrolytes, liver function tests, clotting profile and CRP at baseline, month 3 and month 6.
Procedure: Physical examination
Including cardio-respiratory and abdominal examination at baseline, month 3 and month 6.
Procedure: Vital signs
Height, weight, heart rate, blood pressure and temperature at baseline, month 3 and month 6.
Procedure: Urine pregnancy test
For subjects of child-bearing potential, urine pregnancy test at baseline, month 3 and month 6.
Procedure: Completion of patient diary card
Subjects are requested to complete when study medication is taken and in any new or unusual symptoms are experienced on a daily basis for 6 months.
Placebo Comparator: Placebo Procedure: Endoscopy
At baseline, month 3 and month 6.
Other Names:
  • Colonoscopy
  • Flexible sigmoidoscopy
Procedure: Biopsies taken
9 biopsies taken for measurement of apoptosis (3 biopsies), cell proliferation (3 biopsies) and fatty acid levels (3 biopsies) at baseline, month 3 and month 6.
Procedure: Clinical chemistry
Full blood count at baseline, month 3 and month 6.
Procedure: Haematology
Urea and electrolytes, liver function tests, clotting profile and CRP at baseline, month 3 and month 6.
Procedure: Physical examination
Including cardio-respiratory and abdominal examination at baseline, month 3 and month 6.
Procedure: Vital signs
Height, weight, heart rate, blood pressure and temperature at baseline, month 3 and month 6.
Procedure: Urine pregnancy test
For subjects of child-bearing potential, urine pregnancy test at baseline, month 3 and month 6.
Procedure: Completion of patient diary card
Subjects are requested to complete when study medication is taken and in any new or unusual symptoms are experienced on a daily basis for 6 months.

Detailed Description:

Colorectal cancer is generally accepted to develop from changes within colonic adenomatous polyps. More than 90% of new large bowel cancers arise sporadically. The molecular events leading to the development of colorectal cancer from polyps are characterised by an imbalance in cell proliferation (formation of new cells) and apoptosis (natural cell death) from changes in the genes involved in normal colon cells.

Recent work at St George's Hospital Medical School, London, has shown significant beneficial effects on cell proliferation and apoptosis rates in the lining of the colon in subjects with a history of colonic adenomas using a highly purified, free-fatty acid form of eicosapentaenoic acid (EPA).

Comparator(s): 2g EPA per day for 6 months and 1g EPA per day for 6 months will be compared against placebo for 6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females aged over 18
  • Patients of child-bearing potential must demonstrate a negative pregnancy test at screening, and should use a reliable form of contraception during the trial and for 1 month afterwards, e.g:
  • Oral contraceptive + condom
  • Intra-uterine device (IUD)+ condom
  • Diaphragm with spermicide + condom
  • Male partners of women of child bearing potential should use a reliable form of contraception during the trial and for 1 month afterwards, e.g:
  • Oral contraceptive + condom
  • Intra-uterine device (IUD)+ condom
  • Diaphragm with spermicide + condom
  • Patients must have a known history of colorectal adenomata and be under clinical follow-up for these, or be found to have one or more of these at the time of colonoscopy
  • Patients must have provided written informed consent to participate

Exclusion Criteria:

  • Patients who are allergic to fish
  • Patients who have diabetes mellitus
  • Patients who are pregnant or breast-feeding
  • Patients taking aspirin or other non-steroidal anti-inflammatory drugs on a regular basis
  • Patients who have aspirin-sensitive asthma
  • Patients suffering from haemorrhagic disorders
  • Patients who are taking warfarin or other anticoagulants
  • Patients who have significant abnormalities on their screening blood tests
  • Patients taking lipid lowering medication
  • Patients with known inflammatory bowel disease (IBD), or previously unknown IBD until discovered at the time of their colonoscopy
  • Patients with gastrointestinal malabsorptive disease
  • Patients belonging to a known polyposis syndrome (e.g. FAP, HNPCC)
  • Patients with a previous colonic resection for colorectal cancer
  • Patients who are taking other fish-oil supplements (e.g. cod liver oil) who are unwilling to stop them for the duration of the study
  • Patients who are deemed mentally incompetent, or have a history of anorexia nervosa or bulimia
  • Patients with a history of alcohol or drug abuse, including laxative abuse
  • Patients considered by their physician unlikely to be able to comply with the protocol.
  • Patients who have taken part in an experimental drug study in the preceding 2 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00432913

Locations
Italy
S. Orsola Hospital
Bologna, Italy, 40138
United Kingdom
St. George's Hospital Medical School
London, United Kingdom, SW17 0RE
Sponsors and Collaborators
S.L.A. Pharma AG
Investigators
Principal Investigator: Nicholas J West, MB BS FRCS St. George's Hospital Medical School, London
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00432913     History of Changes
Other Study ID Numbers: EPA/POL/02
Study First Received: February 7, 2007
Last Updated: October 16, 2008
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by S.L.A. Pharma AG:
Eicosapentaenoic acid
EPA
EPA 99%
Fatty acid
omega-3
apoptosis
cell proliferation
colonic mucosa
polyps
adenomatous polyps
endoscopy
PUFA

Additional relevant MeSH terms:
Polyps
Adenomatous Polyps
Pathological Conditions, Anatomical
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on September 18, 2014